Infections caused by Staphylococcus aureus (“S. aureus”) are a major causative agent of hospital and non-hospital infections. These infections cause longer hospitalization time and cost. S. aureus infections range from common, minor skin infections to blood-borne infections of the heart valves called infective endocarditis.
Infective endocarditis may be used as a model for illustrating S. aureus infection. Endocarditis is an inflammation of the endocardium, the inner layer of the heart. In some variations, it involves the heart valves. In other variations it may involve the interventricular septum, the chordae tendineae, the mural endocardium, and even surfaces of implanted medical devices such as intracardiac devices and prosthetic valves.
One characteristic of endocarditis is a lesion, which may also be referred to as a vegetation. A vegetation includes but is not limited to, a mass of platelets, fibrin, microcolonies of microorganisms, and inflammatory cells. In some variations, infective endocarditis vegetations may also include a center of granulomatus tissue, e.g., a collection of the immune cells called macrophages. Granulomatus tissue may fibrose (e.g., form excess tissue) and/or calcify.
Heart valves do not receive dedicated blood supply, which may blunt the immune response, making it difficult for immune defenses (such as white blood cells) to directly reach the valves via the bloodstream. Valves may have an increased susceptibility to infection, e.g. bacterial infection, due to (among other factors) the blunted immune response. The lack of blood supply to the valves may also decrease the effectiveness of traditional treatments, since drugs (e.g., those delivered via bloodstream) also have difficulty reaching infected valves.
S. aureus infection rates continue to increase. S. aureus acute infective endocarditis is 25-47% fatal despite antibiotic therapy. Vancomycin is a common antimicrobial treatment for infections caused by S. aureus (e.g., methicillin resistant S. aureus). Of great concern is the observation that drug resistant strains of S. aureus are rapidly evolving. The rapid spread of hypervirulent, multi-drug resistant strains of S. aureus suggest S. aureus will likely become resistant to all antibiotics and an even greater threat to public health. This threat is exacerbated due to, among other things, the reluctance of drug companies to develop new antibiotics.